Although 80% of human cancer is the result of exogenous environmental agents, very little is known about the molecular mechanism(s) leading to carcinogenicity. Although carcinogenesis might be initiated by a mutational change, it cannot be described by a single mutational event because secondary stages must occur.
Massive changes in the organization of the genomic sequences by relocation and amplification of specific cellular sequences may be a critical step in carcinogenesis.
The design of new short-term bioassays for chemical carcinogens is of current interest. A number of short-term methods for detecting potential chemical carcinogens and mutagens have emerged from diverse areas of cancer research, genetic and molecular biology (Hollstein, M., McCann, J., Angelosanto, F. A. and Nichols, W. W. Mutation Res. 65, 133-226 (1979)).
Because no single assay has yet detected all the carcinogens, a variety of different tests may be required. None of the existing tests for carcinogenicity measure amplification or rearrangement of specific cellular sequences.
Recent studies in our laboratory on the carcinogen-mediated amplification of genomic sequences led us to the development of a model experimental system based on SV40 transformed Chinese hamster embryo cells and a highly sensitive in situ hybridization procedure for the detection of single cells in which viral DNA synthesis is induced.
This procedure enables the determination of the extent of the carcinogen mediated amplification of SV40 DNA sequences. The molecular mechanism leading to this phenomenon is currently unknown. The possibility that the amplification of SV40 DNA sequences is a reflection of a general gene amplification phenomenon is currently being investigated.